363 research outputs found

    A Trial of Philosophy

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    A note on reporting of reservoir 14C disequilibria and age offsets

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    Author Posting. © The Author(s), 2016. This is the author's version of the work. It is posted here for personal use, not for redistribution. The definitive version was published in Radiocarbon 58 (2016): 205-211, doi:10.1017/RDC.2015.22.Reservoir age offsets are widely used to correct marine and speleothem radiocarbon age measurements for various calibration purposes. They also serve as a powerful tracer for carbon cycle dynamics. However, a clear terminology regarding reservoir age offsets is lacking, sometimes leading to miscalculations. This note seeks to provide consistent conventions for reporting reservoir 14C disequilibria useful to a broad range of environmental sciences. This contribution introduces the F14R and δ14R metrics to express the relative 14C disequilibrium between two contemporaneous reservoirs and the R metric as the associated reservoir age offset.G.S. acknowledges the Postdoctoral Scholar Program at the Woods Hole Oceanographic Institution with funding provided by the National Ocean Sciences Accelerator Mass Spectrometry Facility (OCE-1239667). S.R.B acknowledges Dean Minghua Zhang and Provost Dennis Assanis of Stony Brook University for financial support

    A first-in-human study of AMG 208, an oral MET inhibitor, in adult patients with advanced solid tumors.

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    BackgroundThis first-in-human study evaluated AMG 208, a small-molecule MET inhibitor, in patients with advanced solid tumors.MethodsThree to nine patients were enrolled into one of seven AMG 208 dose cohorts (25, 50, 100, 150, 200, 300, and 400 mg). Patients received AMG 208 orally on days 1 and days 4-28 once daily. The primary objectives were to evaluate the safety, tolerability, pharmacokinetics, and maximum tolerated dose (MTD) of AMG 208.ResultsFifty-four patients were enrolled. Six dose-limiting toxicities were observed: grade 3 increased aspartate aminotransferase (200 mg), grade 3 thrombocytopenia (200 mg), grade 4 acute myocardial infarction (300 mg), grade 3 prolonged QT (300 mg), and two cases of grade 3 hypertension (400 mg). The MTD was not reached. The most frequent grade ≥3 treatment-related adverse event was anemia (n = 3) followed by hypertension, prolonged QT, and thrombocytopenia (two patients each). AMG 208 exposure increased linearly with dose; mean plasma half-life estimates were 21.4-68.7 hours. One complete response (prostate cancer) and three partial responses (two in prostate cancer, one in kidney cancer) were observed.ConclusionsIn this study, AMG 208 had manageable toxicities and showed evidence of antitumor activity, particularly in prostate cancer

    Predictors of orbital convergence in primates: A test of the snake detection hypothesis of primate evolution

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    Traditional explanations for the evolution of high orbital convergence and stereoscopic vision in primates have focused on how stereopsis might have aided early primates in foraging or locomoting in an arboreal environment. It has recently been suggested that predation risk by constricting snakes was the selective force that favored the evolution of orbital convergence in early primates, and that later exposure to venomous snakes favored further degrees of convergence in anthropoid primates. Our study tests this snake detection hypothesis (SDH) by examining whether orbital convergence among extant primates is indeed associated with the shared evolutionary history with snakes or the risk that snakes pose for a given species. We predicted that orbital convergence would be higher in species that: 1) have a longer history of sympatry with venomous snakes, 2) are likely to encounter snakes more frequently, 3) are less able to detect or deter snakes due to group size effects, and 4) are more likely to be preyed upon by snakes. Results based on phylogenetically independent contrasts do not support the SDH. Orbital convergence shows no relationship to the shared history with venomous snakes, likelihood of encountering snakes, or group size. Moreover, those species less likely to be targeted as prey by snakes show significantly higher values of orbital convergence. Although an improved ability to detect camouflaged snakes, along with other cryptic stimuli, is likely a consequence of increased orbital convergence, this was unlikely to have been the primary selective force favoring the evolution of stereoscopic vision in primates
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